Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer

Abstract

7086 Background: It has been reported that mutations in epidermal growth factor receptor (EGFR) play a critical role in predicting tumor response in patients receiving gefitinib for non-small cell lung cancer (NSCLC). We investigated the associations of EGFR mutations to tumor response and survival in gefitinib-treated NSCLC patients. Methods: We examined EGFR gene mutations in exons 18, 19 and 21 by DNA sequencing in paraffin-embedded tumor tissues of NSCLC patients who have received gefitinib. The results were correlated with the clinical parameters. Results: Mutations in the tyrosine kinase domain of EGFR were found in 29 of 54 cases (53.7%). Of them, twelve cases had a deletion in exon 19 and seventeen cases had a substitution in exon 18 and/or 21. Mutation was an independent predictor for disease control (P< 0.001) and tumor response (P= 0.020); the positive predictive values were 93% and 75% and negative predictive values were 60% and 65%, respectively. Compared with patients whose tumor bearing non-mutant EGFR, patients with EGFR mutations showed better progression-free survival (median 7.9 m vs. 1.8 m, P< 0.001) and overall survival (median 12 m vs. 4.7 m, P= 0.029). Moreover, in the gefitinib responders, patients with mutations had a longer response duration than patients without mutations (median 9.1 m vs. 2.9 m, P= 0.033). It was unlikely that patients with EGFR mutations in different exons have variable response or survival to gefitinib treatment. Conclusions: EGFR mutations can be used as a predictive and prognostic indicator in patients receiving gefitinib for NSCLC No significant financial relationships to disclose.